The fluidity of the cell membrane and the lateral mobility of membrane components allow small electric fields to move charged membrane components along the cell membrane, a phenomenon termed lateral electromigration. We have hypothesized that longitudinal electric fields, generated by the activity of excitable cells, produce lateral electromigration of membrane components. Thus these fields provide a means to develop, maintain, and modulate the membrane specializations seen in excitable cells. The hypothesis is based upon preliminary findings that: (1) repetitive pulsed electric fields can cause migration of muscle cell surface receptors; (2) repetitive applicaton of acetylocholine, a neurotransmitter, to the surface of a muscle cell can cause a local increase in the sensitivity of the cell to acetylcholine; and (3) steady local electric fields can cause an increase in the peak sodium conductance of a voltage-clamped unmyelinated axon. In order to test this hypothesis, we will extend our preliminary work with electrophysiological and tissue culture techniques to: (1) determine if repetitive local depolarizations of the muscle cell membrane lead to an accumulation of neurotransmitter receptors; (2) determine if repetitive selective usage of one synapse on a muscle cell leads to an accumulation of neurotransmitter receptors to the active synapse by an electromigration mechanism, thus providing a use-dependent modulation of synaptic efficacy; and (3) determine whether biologically relevant electric fields can produce lateral electromigration in two model neuronal systems, leech nueron cell bodies and the crayfish medial giant axon. Our long term goal is to elucidate the cellular mechanisms of neuronal plasticity, with a focus on the organization of the neuronal membrane.